crossing96/oncoscreening huggingface dataset:
Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.	OBJECTIVES: To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer. PATIENTS AND METHODS: The study included 162 patients with pure ureteric cancer who were treated between January 2005 and December 2010 at a single tertiary referral centre. The association between hydronephrosis grade with pathological findings and oncological outcomes was assessed using multivariate Cox regression analysis. RESULTS: Hydronephrosis grade >2 was independently associated with non-organ-confined ureteric cancer (P = 0.003). Hydronephrosis grade <2 was highly prevalent in organ-confined disease. Hydronephrosis grade >2 and bladder cancer history independently predict bladder cancer recurrence (P = 0.021 and P = 0.002, respectively) Hydronephrosis of grade >2 was found to be associated with local and distant recurrence only in univariate analysis; non-organ-confined pathology independently predicted local and distant oncological failure (P ≤ 0.001 and P = 0.002, respectively). CONCLUSIONS: Hydronephrosis grade >2 is associated with non-organ-confined ureteric cancer and with bladder cancer recurrence. Non-organ-confined pathology is still the most important predictor for local and distant oncological failure.	bladder
Synergistic induction of cancer cell death and reduction of clonogenic resistance by cisplatin and FK228.	Human urinary bladder cancer is the fifth most common cancer in the United States, and the long-term disease-free survival in patients is still suboptimal with current chemotherapeutic regimens. Development of effective chemotherapeutic regimens is crucial to decrease the morbidity and mortality of this cancer. The goal of this study was to investigate the effectiveness of FK228 in increasing cisplatin's ability to induce bladder cancer cell death and reduce drug resistance. Our study revealed that FK228 combined with cisplatin synergistically induced cell death and reduced clonogenic survival of human urinary bladder cancer cells. The Erk-Nox pathway played an important role in mediating signals highly increased by this combined treatment to induce significantly-elevated levels of reactive oxygen species, leading to substantially-induced caspase activation and synergistically-increased death in cancer cells. Cisplatin was able to enhance the ability of FK228 to significantly reduce glutathione, indicating a novel activity of combined FK228 and cisplatin in reducing drug resistance. The ability of combined FK228 and cisplatin to synergistically induce cell death and reduce clonogenic survival was also applicable to colon cancer cells. Hence, combined use of FK228 with cisplatin should be considered in development of therapeutic strategies to control urinary bladder cancer and other cancer development and recurrence.	bladder
Severe pneumonia after intravesical BCG instillation in a patient with invasive bladder cancer: case report and literature review.	We present here the case of a 66 year old man with a severe bilateral community acquired pneumonia secondary to dissemination after an intravesical instillation of bacilllus Calmette-Guerin (BCG). Diagnosis was based on positive polymerase chain reaction (PCR) for mycobacterium tuberculosis complex in bronchoalveolar lavage and on the finding on transbronchial biopsy of non necrotising granulomas histopathologically similar to the granulomas found in bladder biopsies. These findings were confirmed using a validated real time PCR assay demonstrating the presence of the BCG genome in transbronchial and bladder biopsies.	bladder
Fruit and vegetable intakes are associated with lower risk of bladder cancer among women in the Multiethnic Cohort Study.	Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer, as they contain numerous nutrients, phytochemicals, and antioxidants with potentially anticarcinogenic properties. In a prospective analysis of 185,885 older adults participating in the Multiethnic Cohort Study, we examined whether the consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with bladder cancer risk. Cox proportional hazards models were used to calculate HRs and 95% CIs for bladder cancer in relation to dietary intakes. A total of 581 invasive bladder cancer cases (429 men and 152 women) were diagnosed over a mean follow-up period of 12.5 y. In women, total fruits and vegetables [HR = 0.35 (95% CI: 0.22, 0.56); highest vs. lowest quartile], total vegetables [HR = 0.49 (95% CI: 0.29, 0.83)], yellow-orange vegetables [HR = 0.48 (95% CI: 0.30, 0.77)], total fruits [HR = 0.54 (95% CI: 0.34, 0.85)], and citrus fruits [HR = 0.56 (95% CI: 0.34, 0.90)] were inversely associated with the risk of invasive bladder cancer in risk factor-adjusted models. In addition, women with the highest intakes of vitamins A, C, and E; the carotenoids α-carotene, β-carotene, and β-cryptoxanthin; and folate had a lower risk of bladder cancer. For men, no associations for fruits, vegetables, or nutrients were found overall, although inverse associations were observed for vegetable intake among current smokers, and in ethnic-specific analyses, for fruit and vegetable intake among Latinos specifically. Our findings suggest that greater consumption of fruits and vegetables may lower the risk of invasive bladder cancer among women and highlight the need for specific subgroup analyses in future studies.	bladder
Cytotoxicity of ferulic Acid on T24 cell line differentiated by different microenvironments.	Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA) is a ubiquitous health beneficial phenolic acid. Although FA has shown a diversity of biological activities including anti-inflammatory, antihypercholesterolemic and anticancer bioactivities, studies revealing its adverse effects are accumulating. Recently, 3D-cultures are shown to exhibit uniquely biological behaviors different from that of 2D cultures. To understand whether the cytotoxicity of FA against the T24 cell line (a bladder cancer cell line) in 2D-culture could consistently retain similar bioactivity if cultured in the 3D-systems, we conducted this experiment with 2 mM FA. Much higher cytotoxicity was found for 3D- than 2D-culture, showing (2D vs. 3D): apoptotic rates, 64% and 76%; cell killing rates, 3.00 × 10(5) cells mmol(-1)·h(-1) and 2.63 × 10(6) cells mmol(-1)·h(-1), attaining a 8.77-fold. FA upregulated the activities at 72 h (2D vs. 3D in folds that of control): SOD, 1.73-folds (P < 0.05) versus 3.18 folds (P < 0.001); and catalase, 2.58 versus 1.33-folds. Comparing to the control (without FA), Bcl-2 was prominently downregulated while Bax, caspase-3 and cleaved caspase-9 were more upregulated in 3D-cultures (P < 0.05). Conclusively, different microenvironments could elicit different biological significance which in part can be ascribed to different mass transport rate.	bladder
Diagnostic value of bladder tumor fibronectin in patients with bladder tumor: a systematic review with meta-analysis.	OBJECTIVES: Bladder tumor fibronectin (BTF) has been related as a promising biomarker for the early diagnosis of bladder tumor. The meta-analysis was used to establish the diagnostic value of bladder tumor fibronectin in diagnosing bladder tumor. METHODS: Relevant literatures evaluating the value of BTF in the diagnosis of bladder tumor were searched in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang Data. Summary estimates were used to evaluate the value of BTF in the diagnosis of bladder tumor by using the Meta-DiSc and STATA 11.0 statistical software. RESULTS: The meta-analysis included 5 studies (649 patients, 291 controls). The summary estimates revealed that the pooled sensitivity was 81% (95% confidence interval [CI]: 74%-85.1%) and specificity was 80% (95%CI 74%-84%). In addition, the area under the summary ROC curve (AUC) was 0.86 (95%CI 0.82-0.89). CONCLUSION: BTF is a potential marker for the diagnosis of bladder tumor, and more prospective studies are needed in the future.	bladder
Bladder preservation therapy for muscle-invading bladder cancers on Radiation Therapy Oncology Group trials 8802, 8903, 9506, and 9706: vascular endothelial growth factor B overexpression predicts for increased distant metastasis and shorter survival.	BACKGROUND: From 1988 to 1999, the Radiation Therapy Oncology Group (RTOG) conducted four prospective studies (8802, 8903, 9506, 9706) of patients with clinical stage T2-4a muscle-invasive bladder cancer. Treatment was selective bladder preservation using transurethral surgery (TURBT) plus cisplatin-based induction and consolidation chemoradiation regimens, reserving radical cystectomy for invasive tumor recurrence. We investigated vascular endothelial growth factor (VEGF) pathway biomarkers in this unique clinical dataset (median follow-up of 3.1 years). METHODS: A total of 43 patients with tissue available from the entry TURBT were included in this analysis. Expression of VEGF ligands and receptors were quantified and scored by the AQUA platform (HistoRX, now Genoptix, Carlsbad, CA) and analyzed after median split. RESULTS: VEGF expression levels were not associated with increased rates of complete response to induction chemoradiation. Higher levels of cytoplasmic VEGF-B, VEGF-C, and VEGF-R2 were associated with decreased overall survival rates. The 3-year overall survival estimates for high and low expressers were 43.7% and 75% for VEGF-B cytoplasm (p = .01), 40.2% and 86.7% for VEGF-C cytoplasm (p = .01), and 49.7% and 66.7% for VEGF-R2 cytoplasm (p = .02). Higher expression levels of cytoplasm VEGF-B were associated with higher rates of distant failure (p = .01). CONCLUSIONS: Although VEGF ligands and receptors do not appear to be associated with complete response to induction chemoradiation for muscle-invasive bladder cancer, we report significant associations with overall survival and distant failure for certain VEGF family members.	bladder
Quantitative changes in p53, Bcl-2 and apoptosis in blood and urine of bladder cancer patients.	BACKGROUND: While current pathological and clinical parameters provide important prognostic information, they still have a limited ability to predict the true malignant potential of most bladder tumors. Therefore, the present study was carried out to investigate the levels of anti-apoptotic proteins such as p53 and Bcl-2, and of apoptosis itself as reflected by the increase in sub-G1 peak staining, in the blood and urine of bladder cancer patients, and to thus determine the usefulness of these parameters as tools for early and accurate prediction of tumor growth and development of metastases, in order to assess treatment benefit potential. METHODS: A total of 80 bladder cancer patients and 50 healthy controls without malignancies were enrolled in this study. The levels of p53, Bcl-2 and apoptosis (sub-G1 peak) were evaluated by flow cytometry in the urine and blood of patients and controls. RESULTS: Levels of p53, Bcl-2 and apoptosis were significantly higher in the urine sediment than in the blood. Moreover, p53 levels in the blood and urine of bladder cancer patients were significantly higher than in controls, and were significantly increased during the development of tumor grades and in association with positive parameters of urine analysis. In contrast, Bcl-2 and apoptosis levels in the blood and urine of bladder cancer patients were significantly lower than in samples from controls, and were significantly decreased during the development of tumor grades and in association with positive parameters of urine analysis. Apoptosis levels were positively correlated with Bcl-2 levels but negatively correlated with p53 levels. CONCLUSIONS: These findings suggest that quantitative analysis of p53, Bcl-2 and apoptosis, especially in the urine sediment, may be a useful tool in the diagnosis of bladder cancer.	bladder
Beclin 1 and bcl-2 expressions in bladder urothelial tumors and their association with clinicopathological parameters.	Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation, as well as in the development and progression of cancer. The aim of this study was to examine the expression of beclin 1 and bcl-2 in bladder urothelial tumors, and to investigate the relationship between these two markers and clinicopathological parameters. Our study included 84 bladder urothelial tumors and 10 non-tumoral bladder tissues. Immunohistochemistry was performed on tissue microarray (TMA) sections and was evaluated semiquantitatively on the basis of the percentage of positively stained cells (proportion) and staining intensity. A significant association was found between the expression score of beclin 1 and pT stages of the urothelial tumors (p=0.012). Also, the level of beclin 1 expression inversely correlated with histological grade and pT stages (p=0.009, r=-0.284; p=0.001, r=-0.361, respectively). The bcl-2 expression level positively correlated with histological grade and pT stages of the urothelial tumors (p=0.026, r=0.243; p<0.0001, r=0.491, respectively). In addition, the level of beclin 1 expression tended to be inversely correlated with the bcl-2 expression level in urothelial tumors (p=0.055, r=-0.210). According to our data, down-regulation of beclin 1 expression and also bcl-2 overexpression seem to play an important role in the progression and aggressiveness of bladder urothelial tumors.	bladder
Relationship between 6- and 9-month progression-free survival and overall survival in patients with metastatic urothelial cancer treated with first-line cisplatin-based chemotherapy.	BACKGROUND: Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with metastatic urothelial carcinoma (UC) is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS). METHODS: Data was pooled from 7 phase 2 and 3 trials evaluating cisplatin-based chemotherapy in metastatic UC. An independent cohort of patients enrolled on a phase 3 trial was used for external validation. Landmark analyses for progression at 6 and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS. RESULTS: A total of 364 patients were included in the initial cohort. The median PFS was 8.21 months (95% confidence interval = 7.43, 8.39) and the median OS was 13.50 months (95% confidence interval = 11.80, 15.67). In the landmark analysis, the median OS for patients who progressed at 6 months was 3.87 months compared with 15.06 months for those patients who did not progress (P < .0001) and the median OS for patients who progressed at 9 months was 5.65 months compared with 21.39 months for those patients who did not progress (P < .0001). A Fleischer model demonstrated a statistically significant dependent correlation between PFS and OS. The findings were externally validated in an independent cohort. CONCLUSIONS: PFS at 6 and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy and could potentially serve as endpoints in (randomized) phase 2 trials to screen the activity of novel regimens.	bladder
[Relative efficacy of neoadjuvant gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management for muscle-invasive bladder cancer].	Systemic cisplatin-based chemotherapy regimens are the gold standard in advanced bladder cancer. Gemcitabine plus cisplatin (GC) therapy has often been used, although there is no significant evidence that it is better than methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy in neoadjuvant chemotherapy. We retrospectively evaluated the relative efficacy of the two chemotherapeutic regimens in the management of muscle-invasive bladder cancer on patients who had had radical cystectomy for clinical stage T2-T4, N and, M0 bladder cancer. Fourteen patients (24.1%) and 44 (75.9%) patients were treated with GC and MVAC therapy, respectively. GC therapy was significantly more effective than MVAC therapy in pathological down-staging (to pT0) rate. On multivariate analysis, the choice of regimen (MVAC) was an independent predictor of the presence of residual cancer after a neoadjuvant chemotherapy. The clinical response to neoadjuvant GC therapy was superior to that to neoadjuvant MVAC therapy. Moreover, GC therapy was associated with less non-hematologic toxicity than MVAC therapy, especially with respect to the occurrence of nausea.	bladder
Green tea polyphenols and cancer chemoprevention of genitourinary cancer.	Green tea, which has higher concentrations of polyphenols than other teas, has been correlated with reduced risk of various malignancies with most data supporting a potential protective role in prostate neoplasia. Preclinical studies over the last 25 years implicate constituent green tea catechins, epigallocatechin-3-gallate (EGCG) being the predominant form, as the main mechanistic ingredient in the observed biologic effects, which vary from proapoptotic effects to inhibition of androgen receptor and signal transduction pathways. There have been few prospective clinical trials of green tea polyphenols (GTP), especially with well-characterized formulations and doses. Although there have been hints of beneficial clinical activity in prostate neoplasia, other studies have raised concerns about the limited bioavailability and very low target-tissue concentrations of GTPs. At present there is no proven role for GTP supplementation in the prevention of genitourinary (GU) malignancies, but novel GTP formulations and further clinical testing may still support a future for GTP supplementation in GU cancer prevention.	bladder
HtrA1 in human urothelial bladder cancer: a secreted protein and a potential novel biomarker.	Our aim was to analyze the expression of the serine protease HtrA1 in human bladder tissue and urine in order to point out its possible association with the presence of urothelial bladder cancer. Bladder tissue and urine specimens from cancer patients with different tumor grades and stages (n = 68) and from individuals with cystitis (n = 16) were collected along with biopsy specimens and urine from healthy individuals (n = 68). For the first time, we demonstrated by immunohistochemistry that HtrA1 protein is produced by bladder urothelium in both physiological and inflammatory conditions, whereas it is not detectable in urothelial cancer cells regardless of tumor grade and stage. A different HtrA1 expression between normal-looking and neoplastic bladder tissue, despite similar HtrA1 mRNA levels, was also found by western blotting, which disclosed the presence of two forms of HtrA1, a native form of ∼50 kDa and an autocatalytic form of ∼38 kDa. Our investigations documented the presence of the two forms of HtrA1 also in urine. The ∼38 kDa form was significantly down-regulated in neoplastic tissue, whereas significantly higher amounts of both HtrA1 forms were found in urine from cancer patients compared with both healthy subjects and patients with cystitis. Our findings suggest that HtrA1 is a downexpressed molecule since an early stage of bladder urothelial carcinoma development and that urinary HtrA1 protein may be considered, if successfully validated, as an early and highly sensitive and specific biomarker for this neoplasia (the sensitivity and specificity of HtrA1 are 92.65% and 95.59%, respectively).	bladder
Maintenance bacillus Calmette-Guérin treatment of non-muscle-invasive bladder cancer: a critical evaluation of the evidence.	CONTEXT: Despite the effectiveness of bacillus Calmette-Guérin (BCG) therapy in non-muscle-invasive bladder cancer (NIMBC) to delay recurrence and disease progression, the evidence supporting maintenance treatment and its optimal duration is unkown. OBJECTIVE: The purposes of this paper are to critically review the evidence supporting the use of maintenance BCG after an initial series of induction instillations and to illustrate the factors contributing to current dilemmas in establishing the optimal duration of BCG treatment. EVIDENCE ACQUISITION: The following terms were used in Medline database searches for original articles published before February 1, 2013: bladder cancer, urothelial cancer, bacillus Calmette-Guérin, maintenance, and induction. All randomized controlled trials and meta-analyses, including those based on indirect comparisons, were evaluated. EVIDENCE SYNTHESIS: Seven randomized studies compared induction BCG plus maintenance to induction alone, with or without retreatment with BCG on recurrence. All but one of these studies were underpowered and the largest study used a broad, composite end point: worsening-free survival. Seven meta-analyses have been conducted, three of which included data from observational cohort studies. They demonstrated the benefit of maintenance BCG to reduce disease recurrence and delay progression compared to various control groups; however, the analyses were based on suboptimal data. Although there is new evidence that 1 yr of maintenance BCG is sufficient treatment in intermediate-risk patients, the optimal duration of BCG maintenance remains unknown. A new randomized trial is proposed, which includes induction BCG with retreatment on recurrence as a control arm, to study this question. CONCLUSIONS: The optimal duration of BCG treatment in patients with NMIBC remains unknown and should be the subject of further studies. We recommend that in addition to 3 yr of maintenance BCG, guideline panels also include 1 yr of therapy and induction BCG with retreatment on recurrence as a possible treatment options for patients with NMIBC, albeit with a lower level of evidence and grade of recommendation.	bladder
Prognostic impact of preoperative hematological disorders and a risk stratification model in bladder cancer patients treated with radical cystectomy.	OBJECTIVES: The present study investigated prognostic indicators, including clinicopathological and preoperative hematological factors, and developed a prognostic factor-based risk stratification model in bladder cancer patients treated with radical cystectomy. METHODS: Data were collected from 249 consecutive bladder cancer patients treated with radical cystectomy without neoadjuvant therapy. Prognostic values of the preoperative hematological parameters, along with the patients' clinicopathological parameters were evaluated. A risk stratification model was developed to predict disease-specific survival after radical cystectomy using the regression coefficients of multivariate analysis. RESULTS: In the multivariate analysis, preoperative hemoglobin and C-reactive protein levels, as well as the pathological factors of T stage, positive surgical margin and lymph node metastasis, were independently predictive of disease-specific survival. Low hemoglobin (<10.5 g/dL), a high C-reactive protein (>0.5 mg/dL), extravesical T stage (≥pT3a) and positive surgical margin were independent predictors of poor disease-specific survival. The risk stratification model showed significant differences in disease-specific survival between the three subgroups. CONCLUSIONS: This is the first report to show the significance of combining preoperative hemoglobin with the pathology of radical cystectomy specimens as an independent predictor for disease-specific survival, and it also represents the largest contemporary series to date demonstrating that two types of preoperative hematological disorders, assessed by hemoglobin and C-reactive protein, are independent predictors in bladder cancer patients treated with radical cystectomy. Our risk stratification model could provide physicians with useful prognostic information for identifying patients who might be candidates for multimodal treatments.	bladder